tbuckley/cabot-search huggingface dataset:
Rewilding of laboratory mice enhances granulopoiesis and immunity through intestinal fungal colonization
Authors: Ying-Han Chen, Frank Yeung, Keenan A. Lacey, Kimberly Zaldana, Jian-Da Lin, Gavyn Chern Wei Bee, Caroline McCauley, Ramya S. Barre, Shen-Huan Liang, Christina B. Hansen, Alexander E. Downie, Kyle Tio, Jeffrey N. Weiser, Victor J. Torres, Richard J. Bennett, P’ng Loke, Andrea L. Graham, Ken Cadwell
Journal: Science Immunology (2023)

The paucity of blood granulocyte populations such as neutrophils in laboratory mice is a notable difference between this model organism and humans, but the cause of this species-specific difference is unclear. We previously demonstrated that laboratory mice released into a seminatural environment, referred to as rewilding, display an increase in blood granulocytes that is associated with expansion of fungi in the gut microbiota. Here, we find that tonic signals from fungal colonization induce sustained granulopoiesis through a mechanism distinct from emergency granulopoiesis, leading to a prolonged expansion of circulating neutrophils that promotes immunity. Fungal colonization after either rewilding or oral inoculation of laboratory mice with Candida albicans induced persistent expansion of myeloid progenitors in the bone marrow. This increase in granulopoiesis conferred greater long-term protection from bloodstream infection by gram-positive bacteria than by the trained immune response evoked by transient exposure to the fungal cell wall component β-glucan. Consequently, introducing fungi into laboratory mice may restore aspects of leukocyte development and provide a better model for humans and free-living mammals that are constantly exposed to environmental fungi.
To pay or not to pay for artificial intelligence applications in radiology
Authors: Franziska Lobig, Dhinagar Subramanian, Michael Blankenburg, Ankur Sharma, Archana Variyar, Oisin Butler
Journal: npj Digital Medicine (2023)

Artificial Intelligence-supported digital applications (AI applications) are expected to transform radiology. However, providers need the motivation and incentives to adopt these technologies. For some radiology AI applications, the benefits of the application itself may sufficiently serve as the incentive. For others, payers may have to consider reimbursing the AI application separate from the cost of the underlying imaging studies. In such circumstances, it is important for payers to develop a clear set of criteria to decide which AI applications should be paid for separately. In this article, we propose a framework to help serve as a guide for payers aiming to establish such criteria and for technology vendors developing radiology AI applications. As a rule of thumb, we propose that radiology AI applications with a clinical utility must be reimbursed separately provided they have supporting evidence that the improved diagnostic performance leads to improved outcomes from a societal standpoint, or if such improved outcomes can reasonably be anticipated based on the clinical utility offered.
Independent Recruitment of Different Types of Phospholipases A2 to the Venoms of Caenophidian Snakes: The Rise of PLA2-IIE within Pseudoboini (Dipsadidae)
Authors: Juan David Bayona-Serrano, Felipe Gobi Grazziotin, David Salazar-Valenzuela, Richard H Valente, Pedro Gabriel Nachtigall, Monica Colombini, Ana Moura-da-Silva, Inacio Loiola Meirelles Junqueira-de-Azevedo
Journal: Molecular Biology and Evolution (2023)

Abstract Snake venoms harbor a wide and diverse array of enzymatic and nonenzymatic toxic components, allowing them to exert myriad effects on their prey. However, they appear to trend toward a few optimal compositional scaffolds, dominated by four major toxin classes: SVMPs, SVSPs, 3FTxs, and PLA2s. Nevertheless, the latter appears to be restricted to vipers and elapids, as it has never been reported as a major venom component in rear-fanged species. Here, by investigating the original transcriptomes from 19 species distributed in eight genera from the Pseudoboini tribe (Dipsadidae: Xenodontinae) and screening among seven additional tribes of Dipsadidae and three additional families of advanced snakes, we discovered that a novel type of venom PLA2, resembling a PLA2-IIE, has been recruited to the venom of some species of the Pseudoboini tribe, where it is a major component. Proteomic and functional analyses of these venoms further indicate that these PLA2s play a relevant role in the venoms from this tribe. Moreover, we reconstructed the phylogeny of PLA2s across different snake groups and show that different types of these toxins have been recruited in at least five independent events in caenophidian snakes. Additionally, we present the first compositional profiling of Pseudoboini venoms. Our results demonstrate how relevant phenotypic traits are convergently recruited by different means and from homologous and nonhomologous genes in phylogenetically and ecologically divergent snake groups, possibly optimizing venom composition to overcome diverse adaptative landscapes.
Systematic review and meta-analysis of the effectiveness of chatbots on lifestyle behaviours
Authors: Ben Singh, Timothy Olds, Jacinta Brinsley, Dot Dumuid, Rosa Virgara, Lisa Matricciani, Amanda Watson, Kimberley Szeto, Emily Eglitis, Aaron Miatke, Catherine E. M. Simpson, Corneel Vandelanotte, Carol Maher
Journal: npj Digital Medicine (2023)

Chatbots (also known as conversational agents and virtual assistants) offer the potential to deliver healthcare in an efficient, appealing and personalised manner. The purpose of this systematic review and meta-analysis was to evaluate the efficacy of chatbot interventions designed to improve physical activity, diet and sleep. Electronic databases were searched for randomised and non-randomised controlled trials, and pre-post trials that evaluated chatbot interventions targeting physical activity, diet and/or sleep, published before 1 September 2022. Outcomes were total physical activity, steps, moderate-to-vigorous physical activity (MVPA), fruit and vegetable consumption, sleep quality and sleep duration. Standardised mean differences (SMD) were calculated to compare intervention effects. Subgroup analyses were conducted to assess chatbot type, intervention type, duration, output and use of artificial intelligence. Risk of bias was assessed using the Effective Public Health Practice Project Quality Assessment tool. Nineteen trials were included. Sample sizes ranged between 25-958, and mean participant age ranged between 9-71 years. Most interventions (n = 15, 79%) targeted physical activity, and most trials had a low-quality rating (n = 14, 74%). Meta-analysis results showed significant effects (all p < 0.05) of chatbots for increasing total physical activity (SMD = 0.28 [95% CI = 0.16, 0.40]), daily steps (SMD = 0.28 [95% CI = 0.17, 0.39]), MVPA (SMD = 0.53 [95% CI = 0.24, 0.83]), fruit and vegetable consumption (SMD = 0.59 [95% CI = 0.25, 0.93]), sleep duration (SMD = 0.44 [95% CI = 0.32, 0.55]) and sleep quality (SMD = 0.50 [95% CI = 0.09, 0.90]). Subgroup analyses showed that text-based, and artificial intelligence chatbots were more efficacious than speech/voice chatbots for fruit and vegetable consumption, and multicomponent interventions were more efficacious than chatbot-only interventions for sleep duration and sleep quality (all p < 0.05). Findings from this systematic review and meta-analysis indicate that chatbot interventions are efficacious for increasing physical activity, fruit and vegetable consumption, sleep duration and sleep quality. Chatbot interventions were efficacious across a range of populations and age groups, with both short- and longer-term interventions, and chatbot only and multicomponent interventions being efficacious.
m6A methylation reader IGF2BP2 activates endothelial cells to promote angiogenesis and metastasis of lung adenocarcinoma
Authors: Han Fang, Qi Sun, Jin Zhou, Huijuan Zhang, Qiong Song, Hua Zhang, Guohua Yu, Ying Guo, Chengyu Huang, Yakui Mou, Chuanliang Jia, Yingjian Song, Aina Liu, Kaiyu Song, Congxian Lu, Ruxian Tian, Shizhuang Wei, Dengfeng Yang, Yixuan Chen, Ting Li, Kejian Wang, Yilan Yu, Yufeng Lv, Ke Mo, Ping Sun, Xiaofeng Yu, Xicheng Song
Journal: Molecular Cancer (2023)

Lung adenocarcinoma (LUAD) is a common type of lung cancer with a high risk of metastasis, but the exact molecular mechanisms of metastasis are not yet understood.This study acquired single-cell transcriptomics profiling of 11 distal normal lung tissues, 11 primary LUAD tissues, and 4 metastatic LUAD tissues from the GSE131907 dataset. The lung multicellular ecosystems were characterized at a single-cell resolution, and the potential mechanisms underlying angiogenesis and metastasis of LUAD were explored.We constructed a global single-cell landscape of 93,610 cells from primary and metastatic LUAD and found that IGF2BP2 was specifically expressed both in a LUAD cell subpopulation (termed as LUAD_IGF2BP2), and an endothelial cell subpopulation (termed as En_IGF2BP2). The LUAD_IGF2BP2 subpopulation progressively formed and dominated the ecology of metastatic LUAD during metastatic evolution. IGF2BP2 was preferentially secreted by exosomes in the LUAD_IGF2BP2 subpopulation, which was absorbed by the En_IGF2BP2 subpopulation in the tumor microenvironment. Subsequently, IGF2BP2 improved the RNA stability of FLT4 through m6A modification, thereby activating the PI3K-Akt signaling pathway, and eventually promoting angiogenesis and metastasis. Analysis of clinical data showed that IGF2BP2 was linked with poor overall survival and relapse-free survival for LUAD patients.Overall, these findings provide a novel insight into the multicellular ecosystems of primary and metastatic LUAD, and demonstrate that a specific LUAD_IGF2BP2 subpopulation is a key orchestrator promoting angiogenesis and metastasis, with implications for the gene regulatory mechanisms of LUAD metastatic evolution, representing themselves as potential antiangiogenic targets.
Engineered circular guide RNAs boost CRISPR/Cas12a- and CRISPR/Cas13d-based DNA and RNA editing
Authors: Xin Zhang, Xinlong Wang, Jie Lv, Hongxin Huang, Jiahong Wang, Ma Zhuo, Zhihong Tan, Guanjie Huang, Jiawei Liu, Yuchen Liu, Mengrao Li, Qixiao Lin, Lian Li, Shufeng Ma, Tao Huang, Ying Lin, Xiaoyang Zhao, Zhili Rong
Journal: Genome biology (2023)

Abstract Background The CRISPR/Cas12a and CRISPR/Cas13d systems are widely used for fundamental research and hold great potential for future clinical applications. However, the short half-life of guide RNAs (gRNAs), particularly free gRNAs without Cas nuclease binding, limits their editing efficiency and durability. Results Here, we engineer circular free gRNAs (cgRNAs) to increase their stability, and thus availability for Cas12a and Cas13d processing and loading, to boost editing. cgRNAs increases the efficiency of Cas12a-based transcription activators and genomic DNA cleavage by approximately 2.1- to 40.2-fold for single gene editing and 1.7- to 2.1-fold for multiplexed gene editing than their linear counterparts, without compromising specificity, across multiple sites and cell lines. Similarly, the RNA interference efficiency of Cas13d is increased by around 1.8-fold. In in vivo mouse liver, cgRNAs are more potent in activating gene expression and cleaving genomic DNA. Conclusions CgRNAs enable more efficient programmable DNA and RNA editing for Cas12a and Cas13d with broad applicability for fundamental research and gene therapy.
The implications of nanodiagnostics and artificial intelligence for detecting oral potentially malignant disorders and oral squamous cell carcinoma
Authors: Wei Liu, Yizhou Wang, Xi Yang, Xuemin Shen, Linjun Shi
Journal: International Journal of Surgery (2023)

Liu, Wei MD; Wang, Yizhou DDS; Yang, Xi MD; Shen, Xuemin DMD; Shi, Linjun DMD Author Information
Artificial intelligence (AI) is paving the way for a critical role in drug discovery, drug design, and studying drug–drug interactions – correspondence
Authors: Sandip Chakraborty, Hitesh Chopra, Shopnil Akash, Chiranjib Chakraborty, Kuldeep Dhama
Journal: International Journal of Surgery (2023)

Chakraborty, Sandip; Chopra, Hitesh; Akash, Shopnil; Chakraborty, Chiranjib; Dhama, Kuldeep Author Information
Programmed death ligand 1, poly adenosine diphosphate ribose polymerase, and vascular endothelial growth factor receptor inhibition: a potential combination regimen for targeting triple-negative breast cancer?
Authors: Maryam Abdul Wahid, Hassan ul Hussain, Hafsa Ghouri, Tarneem Khan, Syeda Tayyaba Rehan, Hassan Mumtaz
Journal: International Journal of Surgery (2023)

Abdul Wahid, Maryam , MBBS; Hussain, Hassan ul , MBBS; Ghouri, Hafsa , MBBS; Khan, Tarneem , MBBS; Rehan, Syeda Tayyaba , MBBS; Mumtaz, Hassan , MBBS, MSPH Author Information
ChatGPT encounters multiple opportunities and challenges in neurosurgery
Authors: Yi-Rui Kuang, Ming-Xiang Zou, Hua-Qing Niu, Bo-Yv Zheng, Tao-Lan Zhang, Bo-Wen Zheng
Journal: International Journal of Surgery (2023)

ChatGPT, powered by the GPT model and Transformer architecture, has demonstrated remarkable performance in the domains of medicine and healthcare, providing customized and informative responses. In our study, we investigated the potential of ChatGPT in the field of neurosurgery, focusing on its applications at the patient, neurosurgery student/resident, and neurosurgeon levels.The authors conducted inquiries with ChatGPT from the viewpoints of patients, neurosurgery students/residents, and neurosurgeons, covering a range of topics, such as disease diagnosis, treatment options, prognosis, rehabilitation, and patient care. The authors also explored concepts related to neurosurgery, including fundamental principles and clinical aspects, as well as tools and techniques to enhance the skills of neurosurgery students/residents. Additionally, the authors examined disease-specific medical interventions and the decision-making processes involved in clinical practice.The authors received individual responses from ChatGPT, but they tended to be shallow and repetitive, lacking depth and personalization. Furthermore, ChatGPT may struggle to discern a patient's emotional state, hindering the establishment of rapport and the delivery of appropriate care. The language used in the medical field is influenced by technical and cultural factors, and biases in the training data can result in skewed or inaccurate responses. Additionally, ChatGPT's limitations include the inability to conduct physical examinations or interpret diagnostic images, potentially overlooking complex details and individual nuances in each patient's case. Moreover, its absence in the surgical setting limits its practical utility.Although ChatGPT is a powerful language model, it cannot substitute for the expertise and experience of trained medical professionals. It lacks the capability to perform physical examinations, make diagnoses, administer treatments, establish trust, provide emotional support, and assist in the recovery process. Moreover, the implementation of Artificial Intelligence in healthcare necessitates careful consideration of legal and ethical concerns. While recognizing the potential of ChatGPT, additional training with comprehensive data is necessary to fully maximize its capabilities.
Can velmanase alfa be the next widespread potential therapy for alpha-mannosidosis?
Authors: Sundus Abdul Ghani, Sheeba Burney, Hassan ul Hussain, Maryam Abdul Wahid, Hassan Mumtaz
Journal: International Journal of Surgery (2023)

Alpha-mannosidosis (AM) is an autosomal recessive lysosomal storage disorder caused by reduced activity of the enzyme alpha-mannosidase. The disease is characterized by immunodeficiency, facial and skeletal abnormalities, impaired hearing, and intellectual disability. The clinical subtype of AM shows considerable variability in an individual, and at present, at least three clinical subtypes are suggested. Diagnosis is made by identification of deficiency of α-mannosidase activity in nucleated cells, like fibroblasts. The children are often born apparently normal as the disease is insidiously progressive, hence making early diagnosis essential. Along with supportive care, long-term therapeutic options include hematopoietic stem cell transplant, bone marrow transplantation, and enzyme replacement therapy. The possible benefits of these procedures must be weighed against the overall risk of procedure-related morbidity and mortality. Velmanase alfa is the first human recombinant form of alpha-mannosidase licensed and available for long-term enzyme replacement therapy. It is approved for treating non-neurologic manifestations of mild to moderate AM. The results obtained from different clinical trials provide evidence of the positive clinical effect of the recombinant enzyme on patients with AM. Different routes of diagnosis and unspecific initial symptoms of the disease lead to a delay in the initiation of treatment, resulting in accumulative morbidity. Thus, there is a dire necessity to create more awareness. Furthermore, additional multiple large-scale trials are needed to evaluate the long-term safety and efficacy of velmanase alfa.
A commentary on ‘Evolutionary patterns and research frontiers in neoadjuvant immunotherapy: a bibliometric analysis’
Authors: Kunming Cheng, Yongbin He, Shuqin Gu, Haiyang Wu, Cheng Li
Journal: International Journal of Surgery (2023)

aDepartment of Intensive Care Unit, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China bSchool of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China cUniversity of North Carolina at Chapel Hill, Chapel Hill, NC, USA dDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA eDepartment of Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China fDepartment of Graduate School, Tianjin Medical University, Tianjin, China gDuke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA hDepartment of Orthopaedic Surgery, Beijing Jishuitan Hospital, Fourth Clinical College of Peking University, Beijing, China iState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China jCenter for Musculoskeletal Surgery (CMSC), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt University of Berlin, and Berlin Institute of Health, Berlin, Germany Kunming Cheng and Yongbin He: These authors have contributed equally to this work and share the first authorship. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Duke University, Durham, NC UNITED STATES. E-mail address: [email protected] (H. Wu) *Corresponding author. Address: E-mail address: [email protected] (C. Li) This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Effective treatment with the selective cytokine inhibitor BNZ-1 reveals the cytokine dependency of T-LGL leukemia
Authors: Jonathan E. Brammer, Karen Ballen, Lubomir Sokol, Christiane Querfeld, Ryotaro Nakamura, Anjali Mishra, Eric M. McLaughlin, David Feith, Nazli Azimi, Thomas A. Waldmann, Yutaka Tagaya, Thomas Loughran
Journal: Blood (2023)

Abstract T-cell large granular lymphocytic leukemia (T-LGLL) is a clonal proliferation of cytotoxic T lymphocytes that can result in severe neutropenia, anemia, and bone marrow failure. Strong evidence from patients and mouse models demonstrate the critical role of interleukin-15 (IL-15) in T-LGLL pathogenesis. BNZ-1 is a pegylated peptide that selectively inhibits the binding of IL-15 and other γc cytokines to their cellular receptor complex, which has demonstrated efficacy in ex vivo T-LGLL cells and transgenic mice in preclinical studies. We conducted a phase 1/2 trial of BNZ-1 in patients with T-LGLL who had hematocytopenias (anemia or neutropenia) and required therapy. Clinical responses were assessed using hematologic parameters (improvement in hematocytopenias) based on response criteria from the Eastern Cooperative Oncology Group 5998 T-LGLL trial. BNZ-1 demonstrated clinical partial responses in 20% of patients with T-LGLL with minimal toxicity and the maximum tolerated dose was not reached. Furthermore, T-LGL leukemic cells showed significantly increased apoptosis in response to BNZ-1 treatment as early as day 2, including in clinical nonresponders, with changes that remained statistically different from baseline throughout treatment (P &amp;lt; .005). We report first-in-human proof that T-LGL leukemic cells are dependent on IL-15 and that intervention with IL-15 inhibition with BNZ-1 in patients with T-LGLL shows therapeutic effects, which carries important implications for the understanding of the pathogenesis of this disease. This trial was registered at www.clinicaltrials.gov as #NCT03239392.
3D Bioprinting in Microgravity: Opportunities, Challenges, and Possible Applications in Space
Authors: Angelique Van Ombergen, Franziska Chalupa‐Gantner, Parth Chansoria, Bianca Maria Colosimo, Marco Costantini, Marco Domingos, Alexandre Dufour, Carmelo De Maria, Jürgen Groll, Tomasz Jungst, Riccardo Levato, Jos Malda, Alessandro Margarita, Christophe Marquette, Aleksandr Ovsianikov, Emma Petiot, Sophia Read, Leonardo Surdo, Wojciech Swieszkowski, Giovanni Vozzi, Johannes Windisch, Marcy Zenobi‐Wong, Michael Gelinsky
Journal: Advanced Healthcare Materials (2023)

Abstract 3D bioprinting has developed tremendously in the last couple of years and enables the fabrication of simple, as well as complex, tissue models. The international space agencies have recognized the unique opportunities of these technologies for manufacturing cell and tissue models for basic research in space, in particular for investigating the effects of microgravity and cosmic radiation on different types of human tissues. In addition, bioprinting is capable of producing clinically applicable tissue grafts, and its implementation in space therefore can support the autonomous medical treatment options for astronauts in future long term and far‐distant space missions. The article discusses opportunities but also challenges of operating different types of bioprinters under space conditions, mainly in microgravity. While some process steps, most of which involving the handling of liquids, are challenging under microgravity, this environment can help overcome problems such as cell sedimentation in low viscous bioinks. Hopefully, this publication will motivate more researchers to engage in the topic, with publicly available bioprinting opportunities becoming available at the International Space Station (ISS) in the imminent future.
Systemic administration of budesonide in pegylated liposomes for improved efficacy in chronic rhinosinusitis
Authors: Bhuvanesh Yathavan, Alexa Ellis, Jolanta Jedrzkiewicz, Nithya Subrahmanyam, Nitish Khurana, Abigail Pulsipher, Jeremiah A. Alt, Hamidreza Ghandehari
Journal: Journal of Controlled Release (2023)